Increases in skin blood flow and sweating are critical responses for humans to appropriately regulate internal temperature during exercise and/or hyperthermic exposure. Wounds, such as burns, can damage the skin requiring removal of the damaged tissue and subsequent skin grafting. Although grafted skin ultimately becomes revascularized, it remains unclear whether this vascular bed will ever contribute to the control of internal temperature through cutaneous vasoconstriction and vasodilation during hypothermic and hyperthermic conditions, respectively. In fact, a limited number of studies showed that individuals with healed burns over 40% of their body had higher rectal temperatures during a hyperthermic challenge relative to non-burned counterparts, suggesting impaired thermal regulatory responses of the burned subjects. However, in those studies the presence or absence of skin grafting, as well as the maturity of the wound/graft, was not controlled. Given the lack of information regarding short and long term consequences of skin grafting with respect to revascularization and reinnervation of the grafted skin, the primary objective of this proposal is to test the hypothesis that autonomic and non-autonomic control of skin blood flow in human split-thickness grafts are initially impaired but return towards normal as the graft matures; while sweating responses remain impaired regardless of graft maturity. Moreover, since the vasculature and sweat ducts of donor sites are disrupted due to skin harvesting, the control of skin blood flow and sweating will also be assessed from these sites. These objectives will be accomplished by performing a series of novel experiments to assess neural and non-neural control of skin blood flow and sweating from subjects with split-thickness skin grafts of varying maturities (i.e. graft procedure performed 5-9, 26-38, 50-62, and 72-86 months prior to study participation). In addition, individuals in the 5-9 month post-graft group will be reassessed yearly throughout the funding period. The information gained from the proposed studies will be valuable to both clinicians and patients towards an understanding of the short and long-term consequences of this surgical procedure. Moreover, this information will provide a benchmark from which responses due to emerging technologies (i.e. synthetic skin, cultured skin, growth factors, etc) could be compared with respect to reinnervation and revascularization of the grafted area. [unreadable] [unreadable]